There is a consensus that cell-mediated immunity is of crucial importance in containing infection with Mycobacterium tuberculosis and probably also in maintaining the disease free state after effective anti-tuberculosis chemotherapy. The convergent epidemic of HIV induced immunosuppression has provided compelling evidence for this, with coinfected patients manifesting a greatly increased frequency of active tuberculosis and possibly and increased relapse rate following treatment when compared with HIV negative patients infected with M. tuberculosis. Another facet of the host/parasite relationship of importance in human disease is the pathological effect of the cellular inflammatory response, which is integral to the immunological reaction and the cause of the well known morbidity of tuberculosis. We hypothesize that the initiation of effective anti-tuberculosis therapy is associated with a shift from a predominant, functionally superfluous Th2 type of response to a protective Th1 type of response. It may be that different clinical presentations of tuberculosis may be associated with different cytokine profiles and with different rates of restoration of protective immunity. A secondary hypotheses is that such immunological relationships are profoundly disturbed in patients co-infected with HIV, even before other clinical aspects of immunosuppression are manifest. Understanding the interrelationships of disease activity and cytokine profiles associated with Th1 and Th2 function would facilitate the development of strategies to modulate the deleterious inflammatory effects while maintaining or optimizing protective immune responses. We are beginning to screen patients for a detailed, descriptive and prospective study of immune responses to M. tuberculosis in patients with newly diagnosed tuberculosis, both with and without HIV co-infection. There will be an emphasis on correlating immunological data with clinical and bacteriological progress.